SPPL2B

signal peptide peptidase like 2B, the group of Peptidase family A22

Basic information

Region (hg38): 19:2328614-2355095

Links

ENSG00000005206

∙ NCBI:56928 ∙ OMIM:608239 ∙ HGNC:30627 ∙ Uniprot:Q8TCT7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPPL2B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPPL2B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			3 clinvar	2 clinvar		5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	3	2	0

Variants in SPPL2B

This is a list of pathogenic ClinVar variants found in the SPPL2B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
19-2334713-A-G	not specified	Likely benign (Nov 05, 2021)	2399926
19-2339960-C-G	not specified	Uncertain significance (Sep 30, 2021)	2358737
19-2339961-T-A	not specified	Likely benign (Sep 30, 2021)	2358738
19-2340135-G-A	not specified	Uncertain significance (Jul 09, 2021)	2345015
19-2353033-C-T	not specified	Uncertain significance (Sep 15, 2021)	2350601

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

Function: FUNCTION: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in ITM2B and TNF processing (PubMed:16829952, PubMed:16829951, PubMed:17965014, PubMed:19114711, PubMed:22194595). Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus (PubMed:16829952, PubMed:16829951). May play a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus processed leader peptide gp18 of the envelope glycoprotein gp130 dependently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852). {ECO:0000269|PubMed:16829951, ECO:0000269|PubMed:16829952, ECO:0000269|PubMed:17965014, ECO:0000269|PubMed:19114711, ECO:0000269|PubMed:22194595, ECO:0000269|PubMed:23132852}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

loftool
rvis_EVS: -0.14
rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

pHI: 0.139
hipred: Y
hipred_score: 0.702
ghis

Essentials

essential_gene_CRISPR
essential_gene_CRISPR2
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.341

Mouse Genome Informatics

Gene name: Sppl2b
Phenotype: immune system phenotype; hematopoietic system phenotype;

Gene ontology

Biological process: membrane protein ectodomain proteolysis;regulation of tumor necrosis factor-mediated signaling pathway;membrane protein intracellular domain proteolysis;membrane protein proteolysis;regulation of immune response
Cellular component: Golgi membrane;nucleoplasm;lysosomal membrane;centrosome;plasma membrane;endosome membrane;actin cytoskeleton;membrane;Golgi-associated vesicle membrane;integral component of cytoplasmic side of endoplasmic reticulum membrane;integral component of lumenal side of endoplasmic reticulum membrane
Molecular function: protein binding;aspartic endopeptidase activity, intramembrane cleaving;protein homodimerization activity